Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

Molecules

Luana da S. M. Forezi³  Nathalia M. C. Tolentino³  Alessandra M. T. de Souza⁵  Helena C. Castro²  Raquel C. Montenegro⁴  Rafael F. Dantas¹  Maria E. I. M. Oliveira¹  Floriano P. Silva¹  Leilane H. Barreto⁴  Rommel M. R. Burbano⁴  Bárbara Abrahim-Vieira⁵  Riethe de Oliveira⁵  Vitor F. Ferreira³  Anna C. Cunha³  Fernanda da C. S. Boechat³ 

[1] Laboratory of Biochemistry of Proteins and Peptides, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, RJ, Brazil;LABIEMol, Outeiro de São João Batista, Fluminense Federal University, s/n, Niterói 24020-141, RJ, Brazil;Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil;Institute of Biological Sciences, Federal University of Pará, Av. Augusto Corrêa, n.01—Guamá, Belém, 66075-110, Pará, Brazil;Laboratory of Molecular Modeling & QSAR (ModMolQSAR), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21949-900, RJ, Brazil

关键词: 4-oxoquinoline;    carboxamide;    heterocycles;    anticancer;   

DOI  :  10.3390/molecules19056651

来源: mdpi

【 摘 要 】

As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.